The dynamics of a drop on a mesoscopic scale is investigated by using the many-body dissipative particle dynamic (MDPD) method. The formation of liquid-vapor coexistence interface in the MDPD system is explored. The simulations of the pressure inside/outside the drop and the surface tension are carried out, and it is verified that Laplace’s law is satisfied in our simulation. Different contact angles are obtained by changing conservative interaction parameters between particles. The relationship between MDPD paremeters and contact angles is discussed. Based on the results, the flow behaviors of a drop moving in grooved microcannels are simulated. The results in this paper are useful in studying the fluid with free surfaces flow behavior on rough surface.